Table 2 Preclinical studies using copper-64 as therapeutic agent

[⁶⁴Cu][Cu(ATSM)]

Colon cancer

High dose (370 MBq) of [⁶⁴Cu][Cu(ATSM)] significantly increased the survival rate for tumor bearing animals with no acute adverse effects.

[46]

[⁶⁴Cu][Cu(ATSM)]

Lung cancer

[⁶⁴Cu][Cu(ATSM)] highly accumulated in hypoxic region of the tumor and reduced the survival rate of clonogenic tumor cells in a dose-dependent manner, with observed DNA damage from copper-64 radiation.

[48]

[⁶⁴Cu][Cu(ATSM)]

Lung cancer

Cells in high [⁶⁴Cu][Cu(ATSM)] regions were quiescent but highly clonogenic under mild hypoxia. These cells should be attacked by either [⁶⁴Cu][Cu(ATSM)] internal radiotherapy and/or other intensive-modulated radiotherapy.

[19]

[⁶⁴Cu][Cu(ATSM)]

Breast cancer (MCF-7)

Uptake of [⁶⁴Cu][Cu(ATSM)] as well as radio toxicity increased with decreased atmospheric oxygen level. Statistically significant increase of [⁶⁴Cu][Cu(ATSM)] DNA damage in hypoxia confirmed by Comet assay. Hypoxia-enhanced uptake of copper-64 may be used to overcome radio-resistance of hypoxic MCF-7 cells.

[51]

[⁶⁴Cu][Cu(ATSM)]

Colon cancer

[⁶⁴Cu][Cu(ATSM)] treatment inhibited tumor growth and reduced tumor volume. Percentage of CD133⁺ cancer stem cells and metastatic ability in treated cells were decreased.

[57]

[⁶⁴Cu]CuCl₂

Brain cancer (GBM)

Treatment with [⁶⁴Cu]CuCl₂ inhibited the neurosphere-forming ability of GBM cell lines. A therapeutic dose led to significant decreased of complete regression of tumor volume, followed by prolonged survival with no significant adverse effects observed.

[29]

[⁶⁴Cu][Cu(ATSM)]

Colon cancer

[⁶⁴Cu][Cu(ATSM)] can be used to address the effects of tumor hypoxia and increased HIF-1 activation caused by repeated use of bevacizumab, which has been shown to inhibit tumor growth and prolong survival in bevacizumab-treated mice.

[64]

[⁶⁴Cu][Cu(ATSM)]

Brain cancer (GBM)

Single administration of high-dose (148 MBq) [⁶⁴Cu][Cu(ATSM)] inhibited tumor growth and prolonged survival in a dose-dependent manner, with slight adverse effects. Multiple administration (4 × 37 MBq) showed optimal results for tumor inhibition and survival, with no observed adverse effects.

[62]

[⁶⁴Cu][Cu(ATSM)]/[⁶⁴Cu]CuCl₂

[⁶⁴Cu][Cu(ATSM)] and [⁶⁴Cu]CuCl₂ shown similar in vivo accumulation in the hypoxic regions of the tumor, while [⁶⁴Cu][Cu(ATSM)] also stained non-hypoxic regions with high expression of copper transporters. In vitro [⁶⁴Cu][Cu(ATSM)] has siginificant higher accumulation than [⁶⁴Cu]CuCl₂.

[68]